Cocaine can generate a stronger conditioned reinforcer than food despite being a weaker primary reinforcer

The present study aimed to test the hypothesis that cues associated with drug-taking behavior become extra strong motivators of behavior compared to cues paired with non-drug reinforcers. In Experiment 1, rats were trained to lever press for intravenous cocaine infusions and grain pellets. Each reinforcer was paired with a distinct audiovisual cue. When allowed to choose between these alternatives, rats chose grain on ~70–80% of trials. However, after extinguishing lever pressing, reintroduction of press-contingent cues during a test for cue-induced reinstatement generated more cocaine seeking than grain seeking (also observed on 3- and 8-week follow up tests). To examine whether the same pattern of results would occur with two non-drug reinforcers, Experiment 2 replicated Experiment 1 using grain and sucrose as reinforcement alternatives. Rats chose sucrose over grain on ~70–80% of choice trials and also responded more for the sucrose cue than for the grain cue on the reinstatement test. The disconnect between primary and conditioned reinforcement in Experiment 1 but not Experiment 2, suggests that drug cues may become exceptionally strong motivators of drug-seeking. These results are consistent with cue-focused theories of addiction and may offer insight into the persistent cue-driven drug-seeking behavior observed in addiction.